Over the last two years we have been conducting a double blind placebo controlled trial of Towne strain live cytomegalovirus vaccine in renal transplant candidates. The data accumulated thus far indicate that the vaccine prevents severe CMV disease, but not infection. This appears to be true despite the fact that the vaccinees are immunosuppressed. The current grant request is first for funds to allow the completion of the study: i.e., to enable the accumulation of sufficient numbers of patients to confirm statistical significance of protection, to allow for analysis of subgroups, and to allow for collection of data on long-term safety and persistence of immunity. In addition, booster effects in naturally immune subjects will also be studied. Up to this point, we have used lymphocyte proliferation as the assay of cellular immunity to CMV in the next period we will add newly developed assays of natural killer cell activity and of cytotoxic T cells. If we prove that artificially-induced immunity can be protective, and taking into account possible objections to live virus vaccine, we will extend our vaccine studies to glycoprotein preparations. With the aid of affinity chromatography using monoclonal antibodies to neutralizing glycoproteins we will purify antigens for use in immunization studies. The initial immunizations will be done in guinea pigs, to confirm our earlier work on subunit vaccine, followed by clinical trials in man. Since one of the long range objectives of this work is to develop a vaccine for immunization of normal women for the prevention of congenital disease, it is important to test the efficacy of Towne in immunologically normal individuals. In order to provide a uniform challenges, a pool of low-passage wild CMV has been prepared and safety-tested. A population of cloistered monks have volunteered to be immunized and then to be given the long passage virus as a test of the efficacy of vaccination in normal subjects. These efforts are all directed towards finding an effective immunologic strategy for the prevention of disease caused by CMV.